Raosaheb K. Kale

Usnic Acid Inhibits Growth and Induces Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma A549 Cells

Usnic acid (UA) is a secondary metabolite abundantly found in lichens. Some studies have shown the anticancer potential of UA; however, its efficacy and associated mechanisms are yet to be fully explored. Herein, we assessed the anticancer potency and associated molecular alterations by UA in human lung carcinoma A549 cells. UA treatment (25–100 μM) for 24 and 48 h decreased total cell number by 39–67% (P < 0.01) and 68–89% (P < 0.001), respectively, and enhanced cell death by up to twofold and eightfold (P < 0.001), respectively. UA (1–10 μM) also significantly (P < 0.001) suppressed colony formation of A549 cells. The cell growth inhibition was associated with cell cycle arrest at G0/ G1 phase. UA decreased the expression of cyclin-dependent kinase (CDK)4, CDK6, and cyclin D1 and increased the expression of CDK inhibitor (CDKI) p21/cip1 protein. While examining the cell death associated molecular changes, we observed that UA induces mitochondrial membrane depolarization and led to more than twofold increase (P < 0.01) in apoptotic cells. The apoptotic effect of UA was accompanied by enhanced poly(ADP-ribose) polymerase cleavage. This study shows that UA inhibits cell growth involving G0/G1 phase cell cycle arrest and induces cell death via mitochondrial membrane depolarization and induction of apoptosis in human lung carcinoma cells.

Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells.

Sodium butyrate (NaBt) is the byproduct of anaerobic microbial fermentation inside the gastro-intestinal tract that could reach up to 20mM, and has been shown to inhibit the growth of various cancers. Herein, we evaluated its effect on mitochondrial fusion and associated induction of apoptosis in colorectal cancer cells (CRC). NaBt treatment at physiological (1-5mM) concentrations for 12 and 24h decreased the cell viability and induced G2-M phase cell cycle arrest in HCT116 (12h) and SW480 human CRC cells. This cell cycle arrest was associated with mitochondria-mediated apoptosis accompanied by a decrease in survivin and Bcl-2 expression, and generation of reactive oxygen species (ROS). Furthermore, NaBt treatment resulted in a significant decrease in the mitochondrial mass which is an indicator of mitochondrial fusion. Level of dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission and fusion where its up-regulation correlates with fission, was found to be decreased in CRC cells. Further, at early treatment time, DRP1 down-regulation was noticed in mitochondria which later became drastically reduced in both mitochondria as well as cytosol. DRP1 is activated by cyclin B1-CDK1 complex by its ser616 phosphorylation in which both cyclin B1-CDK1 complex and phospho-DRP1 (ser616) were strongly reduced by NaBt treatment. DRP1 was observed to be regulated by apoptosis as pan-caspase inhibitor showing rescue from NaBt-induced apoptosis also caused the reversal of DRP1 to the normal level as in control proliferating cells. Together, these findings suggest that NaBt can modulate mitochondrial fission and fusion by regulating the level of DRP1 and induce cell cycle arrest and apoptosis in human CRC cells.

Radio-modulatory effects of Green Tea Catechin EGCG on pBR322 plasmid DNA and murine splenocytes against gamma-radiation induced damage

Green tea is rich in polyphenols, like catechins, which are thought to contribute to the health benefits of tea. The aim of this study was to evaluate the radioprotective effect of EGCG (epigallocatechin-3-gallate), a green tea catechin on γ-radiation induced cell damage. Under acellular condition of radiation exposure, pBR322 plasmid DNA was protected by EGCG in a concentration dependent manner. Treatment of murine splenocytes with EGCG 2h prior to radiation (3Gy), protected the cellular DNA against radiation-induced strand breaks. EGCG also inhibited γ-radiation induced cell death in splenocytes. EGCG pretreatment to the cells decreased the radiation induced lipid peroxidation and membrane damage. The levels of phase II enzymes, glutathione and lactate dehydrogenase were restored with EGCG treatment prior to radiation. Our results show that pretreatment with EGCG offers protection to pBR322 DNA under acellular condition and normal splenocytes under cellular condition, against γ-radiation induced damage and is better radioprotector in comparison to quercetin and vitamin C.

Synthesis, characterization, EDX, thermal, antioxidant, antibacterial, topographical, and gas adsorption studies of supramolecular tetraammoniumplatinate

Reaction of K2PtCl4 with N-alkyl-N-benzyl-N,N-dimethyl ammonium chloride (n = 8, 10, 12 and 14 for alkyl) yielded supramolecular bis(benzyldimethylalkylazaniumyl) tetrachloroplatinumdiuide (metallobenzalkonium8 (MBK8), MBK10, MBK12, MBK14) characterized with spectroscopic and energy dispersive X-ray techniques. X-ray difraction powder analysis was performed which confirmed the crystalline nature of the compound. UV/Vis study performed in dimethylformamide, dimethylsulphoxide (DMSO)/H2O, and DMSO/phosphate buffers under physiological conditions show stability of the supramolecular units, with [PtCl4]2−. Zeta potential with particle size distribution of MBK8 obtained with DLS-confirmed agglomeration of the coordinate units. Thermal analysis by differential scattering calorimetric showed an effect of alkyl chain on their heat retention. For MBK8, topographical analysis and specific surface area were investigated with atomic force microscopy and nitrogen adsorption method, illustrating an outstanding alignment in arrays of ionic units, and an extent of apparent cross-sectional areas, respectively. Antioxidant and antibacterial activities were determined with 1–2,5-diphenyl-2-picrylhydrazyl-scavenging effect and Gram-positive and Gram-negative bacteria, respectively. The compounds exhibited activities for both scavenging and bacteria.

Chemopreventive Effect of Lagenaria siceraria in Two Stages DMBA Plus Croton Oil Induced Skin Papillomagenesis

Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer.

Introduction to Special Issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer–An International Journal

The advance of technology and understanding of the process of cancer development suggests that the reported lesser incidence and death due to cancer in countries other than the Western and European countries might also be due to under- diagnosed and under-represented cases. Further, increases in life span as well as ignorance about the disease puts populations in South and South East Asian countries at higher risk to develop cancer. With the increasing rate of cancer incidence every year in non -Western countries, cancer is estimated to become the deadliest disease in coming decades. Conventional chemo- and radio-therapies during the past three decades have not been able to contain the disease, and also have serious side effects. Many natural agents, especially small molecules from plants are non-toxic, easily available and may have anticancer potential. Thus, screening phytochemicals as anticancer agents could be a better approach in cancer prevention and treatment. This chemoprevention approach may have translational significance for prevention and treatment of cancer. Therefore to emphasize the potential role of phytochemicals in cancer prevention and therapy, it was our privilege to host the International Symposium on Recent Advances in Cancer Research: Therapeutics to Chemoprevention, at Central University of Gujarat (CUG), Gandhinagar. The conference was co-organized by the University of Colorado Denver, USA; University of Pittsburgh, USA; University of Oklahoma, USA, during 8–9 February, 2012. Modern biological strategies, specifically the latest developments for the targeted prevention and treatment of cancer via dietary, natural and synthetic agents were discussed in detail. The symposium also emphasized the translational aspect of cancer chemoprevention strategies for various cancers. The symposium deliberations include the ideas for combinatorial chemoprevention by phytochemicals as a promising approach for cancer control and emerging trends for the use of herbal radio-modulators to sensitize the cancer cells for apoptotic cell death. Many bioactive phytochemicals such as silibinin, benzyl isothiocyanate, anthocyanidins, nexrutine, tocopherol, etc. were discussed for their in vivo efficacy in animal tumor models, associated mechanisms and translational potential. Targeting tumor microenvironment with small molecules was found promising and having translational potential for prostate and breast cancer chemoprevention. The novel work and ideas presented at the symposium were helpful in guiding the research orientation of scientists, especially the young researchers who will be benefitted at all levels of their career development. Since chemoprevention of cancer is becoming an attractive approach for controlling cancer, we felt that the deliberations of this symposium should reach to the wider section of the researchers. Therefore, it was planned to bring out a special issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer – An International Journal. We appreciate the researchers for contributing their novel work and ideas to this special issue. We are grateful to the Editor of Nutrition and Cancer – An International Journal, for his initiative to bring out this special issue on this relevant topic. We believe that this volume will be enlightening for the researchers working in the area of cancer chemoprevention.

Surfactant-catalyzed SiO2 thin films preparation and characterization

SiO2 thin films are in high demand for wide range of applications including microelectronics, optoelectronics, solar energy conversion, photocatalysis, and self-cleaning coatings. The performance of thin film is strongly influenced by surface properties like surface roughness, thickness, morphology, wetting behavior, and thermal stability. In these applications, the SiO2 sols were prepared using tetraethylorthosilicate as a source of SiO2 and deposited on 100 × 40 × 2 mm3 glass slide using dip-coating method for 2 min and calcined at 250 °C for 30 min. The SiO2 thin films were obtained using DTAB, SDS, and Tween 20 (Tw 20) surfactants with the thickness of 36.92, 47.15, and 52.39 nm, respectively. Surface morphology was studied with AFM and surface roughness was depicted with 0.9528, 3.6534, and 0.9294 nm. Contact angle measurements have been performed with goniometer to evaluate the wetting behavior of the film. The contact angle of 58.01°, 48.40°, and 37.88° was observed with SDS, DTAB, and Tw 20 film, respectively. The SiO2 thin films with SDS showed more surface roughness and water repelling ability when compared to DTAB and least with Tw 20.

New Materials for Biosensor Construction

Currently materiel development and characterization have attained a central position in science and technology to meet out conventional and unconventional challenges in exponentially growing demands of civil society. Science, technology and society now are closely correlated to serve mutually where materials sever as most fundamental interface and initiator for dedicated and non-dedicated applications. Materials are most significant entities which constitute body of all objective things may be living or non-living being on the basis of structural stability. The structural components which develop binding forces are critical components of the materials. The materials are of two basic categories such as non-molecular and materials molecular. Of course, under nonmolecular materials (NMM), the composites, blends, alloys, eutectic mixtures, acoustic materials constitute most industrially useful sensors mainly for non-biocompatible applications. However, some of them serve as a most biocompatible material such as polymer blends as contact less, stainless steel as bone substitute to normalize a function of bone when it fractures. The NMM serve as basic materials for communication, building materials, machine materials, computer ware materials and many others.

Cell-Death—Inducing Mechanisms of Cancer Chemopreventive Agents

Our increasing knowledge about health and disease suggests that vegetarian diets rich in fruits and vegetables have a significant impact in prevention and therapy of multiple types of cancer. Phytochemicals from both dietary and nondietary origins inhibit cancer growth and progression of human cancers by interacting at the cellular and molecular levels. The mitochondrion is the key organelle that provides energy to cells for their growth and survival. In addition, mitochondria play an important role in cancer cell apoptosis and may also regulate autophagy. Cancer cells have high proliferative and less apoptotic activities; therefore, agents that induce apoptosis selectively in cancer cells are desired for the treatment of cancer. Some dietary phytochemicals target mitochondria causing destruction of mitochondrial membranes leading to the discharge of proapoptotic mitochondrial protein, which initiates apoptotic cell death in cancer. Although the role of autophagy is debated as a mechanism of cell death or cell survival, many phytochemicals modulate autophagy in cancer cells. Therefore, selective targeting of cell-death pathways by phytochemicals in cancer cells could be an attractive strategy for the prevention and treatment of cancer.